In general, an ion trap mass spectrometer works by trapping ions such that the trapped ions undergo oscillatory motion, e.g. backwards and forwards along a linear path or in looped orbits.
An ion trap mass spectrometer may produce a magnetic field, an electrodynamic field or an electrostatic field, or combination of such fields to trap ions. If ions are trapped using an electrostatic field, the ion trap mass spectrometer is commonly referred to as an “electrostatic” ion trap mass spectrometer.
For the avoidance of any doubt, in this disclosure the terms “mass” and “mass/charge ratio” may be used interchangeably. The term “ion” may be used to refer to an ion or any other charged particle.
In general, the frequency of oscillation of trapped ions in an ion trap mass spectrometer is dependent on mass/charge ratio of the ions, since ions with large mass/charge ratios generally take longer to perform an oscillation compared with ions with small mass/charge ratios. Using an image charge/current detector, it is possible to obtain, non-destructively, an image charge/current signal representative of trapped ions undergoing oscillatory motion in the time domain. This image charge/current signal can be converted to the frequency domain e.g. using a Fourier transform (“FT”). Since the frequency of oscillation of trapped ions is dependent on mass/charge ratio, an image charge/current signal in the frequency domain can be viewed as mass spectrum data providing information regarding the mass/charge ratio distribution of the ions that have been trapped.
The inventors have observed that an image charge/current signal obtained using an ion trap mass spectrometer is often not perfectly harmonic. In other words, an image charge/current signal obtained using an ion trap mass spectrometer often has a non-harmonic waveform (e.g. having the form of sharp pulses) in the time domain, which can result in the image charge/current signal having a plurality of harmonics in the frequency domain.
When an image charge/current signal representative of trapped ions having different mass/charge ratios undergoing oscillatory motion in the time domain is converted into a frequency spectrum corresponding to the charge/current signal in the frequency domain, e.g. using a Fourier transform, the image charge/current signal can be represented as a series of peaks in the frequency spectrum, where for trapped ions that have a single mass/charge ratio there is a corresponding set of peaks. A peak in the set has a fundamental frequency corresponding to that mass/charge ratio, and each of the remaining peaks in the set have a respective frequency that is a (second or higher order) harmonic of that fundamental frequency. If the trap contains a plurality of ions with different mass/charge ratios, each mass/charge ratio may be represented by a respective set of peaks in the frequency spectrum and peaks from different sets (i.e. corresponding to different mass/charge ratios) may overlap. Overlapping harmonic peaks in the frequency spectrum can make it difficult to obtain useful information regarding the mass/charge ratio distribution of trapped ions without limiting the range of mass/charge ratios of ions used to obtain the image charge/current signal. Further understanding of these issues can be found in Reference [2] (with particular reference to FIG. 1 of this document).
Methods that attempt to address these difficulties are set out in References [1]-[3] as set out in the References section, below.
All of References [1]-[3] deal with the processing of a complex signal composed of a combination of image current signals each of which is produced by a certain number of ions of the same mass/charge ratio moving in an electrostatic ion trap (EIT) mass analyser. The aim of the processing is to determine the mass/charge ratios of those ions and their relative abundance. Below are very brief descriptions of the main ideas behind these methods.
Reference [1]: This article describes an Orthogonal Projection Method (“OPM”). Conceptually the OPM is concerned with finding the ‘best fit’ approximation of a test signal with a linear combination of a predetermined set of the so-called basis signals. The basis signals are not necessarily orthogonal to each other, which means their scalar products are not 0. According to this method, image current signals of ions with certain mass numbers are adopted as the basis signals that could be viewed as a set of basis vectors {x1, x2, . . . , xm} in some vector space V. The image current signal of the test ions, v, could be orthogonally projected onto these basis vectors. This orthogonal projection, v0, is the ‘best-fit’ approximation of the signal v in the vector space V. v0 could be uniquely expressed by a linear combination of the basis vectors as v0=Σj=1mαj*xj. In this method the mass numbers of ions corresponding to the basis vectors xj are closely and evenly spaced across a mass range of interest, so the coefficients αj could indicate the amount (relative abundance) of the tested ions.
Reference [2]: This document discloses a method in which a linear combination of N image current signals, N≥2, obtained from N image charge/current detectors is used to eliminate N−1 harmonics in a complex multi-harmonic Fourier spectrum. The coefficients of the linear combination are calculated using N calibration image current/charge signals produced by ions of a known mass/charge ratio. Fourier spectra of single mass/charge ratio signals contain only one fundamental frequency and the identification of its harmonics is straightforward. With N independent Fourier spectra of the N image current signals (typically obtained from N image charge/current detectors) it is easy to find their linear combination where only one of the N harmonics is non-zero while the other N−1 harmonics are zero. The coefficients of this linear combination are determined by the instrument's geometry and therefore can be used to create a similar linear combination of other test image current signals acquired by the same instrument. When the test image current signals obtained from different pickup detectors (or their Fourier spectra) are multiplied by the corresponding coefficients and then added together the Fourier spectrum of the resulting signal will not contain N−1 of its harmonics. For example, with only two pickup detectors it is possible to eliminate only one harmonic. If we aim at eliminating the second harmonic leaving the first (the fundamental frequency) then all of the peaks in Fourier spectra with frequencies ranging from the minimal mass fundamental frequency up to the third harmonic of this frequency will be only first harmonics. This allows one to quickly detect all of the ion mass/charge ratios corresponding to this frequency range.
Reference [3]: In this article, a method is proposed for the frequency analysis of data acquired from an EIT analyser. By using comb functions with different time offsets to sample raw image current signals obtained from several different pickup detectors, and by comparing with the standard Fourier transform, a spectrum containing only fundamental frequencies could be obtained.
The image current from an EIT analyser is not perfectly harmonic and the Fast Fourier Transform technique of such a signal generates a set of harmonics for each single mass/charge ratio. Multiple harmonics make it very difficult to obtain the true mass spectrum when many different masses of ions are compounded together. The problem to be solved here is not only to discover the masses of different ion species in a spectrum, but also to find their intensities.
Previously developed peak detection methods for an EIT analyser (see e.g. References [1]-[3]) had a number of disadvantages, such as lower mass range and lower resolving power; none of the methods allowed reasonably accurate calculations of ion abundancies. Some of those disadvantages could be mitigated by utilizing more sophisticated (and therefore more expensive) modifications of the EIT analyser's hardware. However, even then the methods produced results that concealed one or more of the performance characteristics of the EIT analyser.
The present invention has been devised in light of the above considerations.